Dataset Information

Bridging the survival gap in cystic fibrosis: An investigation of lung transplant outcomes in Canada and the United States.

ABSTRACT:

Background

Previous literature in cystic fibrosis (CF) has shown a 10-year survival gap between Canada and the United States (US). We hypothesized that differential access to and survival after lung transplantation may contribute to the observed gap. The objectives of this study were to compare CF transplant outcomes between Canada and the US and estimate the potential contribution of transplantation to the survival gap.

Methods

Data from the Canadian CF Registry and the US Cystic Fibrosis Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. The probability of surviving after transplantation between 2005 and 2016 was calculated using the Kaplan‒Meier method. Survival by insurance status at the time of transplantation and transplant center volume in the US were compared with those in Canada using Cox proportional hazard models. Simulations were used to estimate the contribution of transplantation to the survival gap.

Results

Between 2005 and 2016, there were 2,653 patients in the US and 470 in Canada who underwent lung transplantation for CF. The 1-, 3-, and 5-year survival rates were 88.3%, 71.8%, and 60.3%, respectively, in the US compared with 90.5%, 79.9%, and 69.7%, respectively, in Canada. Patients in the US were also more likely to die on the waitlist (p < 0.01) than patients in Canada. If the proportion of who underwent transplantation and post-transplant survival in the US were to increase to those observed in Canada, we estimate that the survival gap would decrease from 10.8 years to 7.5 years.

Conclusions

Differences in waitlist mortality and post-transplant survival can explain up to a third of the survival gap observed between the US and Canada.

SUBMITTER: Stephenson AL

PROVIDER: S-EPMC7925420 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Bridging the survival gap in cystic fibrosis: An investigation of lung transplant outcomes in Canada and the United States.

Stephenson Anne L AL Ramos Kathleen J KJ Sykes Jenna J Ma Xiayi X Stanojevic Sanja S Quon Bradley S BS Marshall Bruce C BC Petren Kristofer K Ostrenga Joshua S JS Fink Aliza K AK Faro Albert A Elbert Alexander A Chaparro Cecilia C Goss Christopher H CH

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 20201207 3

<h4>Background</h4>Previous literature in cystic fibrosis (CF) has shown a 10-year survival gap between Canada and the United States (US). We hypothesized that differential access to and survival after lung transplantation may contribute to the observed gap. The objectives of this study were to compare CF transplant outcomes between Canada and the US and estimate the potential contribution of transplantation to the survival gap.<h4>Methods</h4>Data from the Canadian CF Registry and the US Cystic ...[more]

PMID: 33386232

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Project description:BackgroundUnderstanding how health outcomes differ for patients with advanced cystic fibrosis (CF) lung disease living in the United States compared with Canada has health policy implications.Research questionWhat are rates of lung transplant (LTx) and rates of death without LTx in the United States and Canada among individuals with FEV1 < 40% predicted?Study design and methodsThis was a retrospective population-based cohort study, 2005 to 2016, using the US CF Foundation, United Network for Organ Sharing, and Canadian CF registries. Individuals with CF and at least two FEV1 measurements < 40% predicted within a 5-year period, age ≥ 6 years, without prior LTx were included. Multivariable competing risk regression for time to death without LTx (LTx as a competing risk) and time to LTx (death as a competing risk) was performed.ResultsThere were 5,899 patients (53% male) and 905 patients (54% male) with CF with FEV1 < 40% predicted living in the United States and Canada, respectively. Multivariable competing risk regression models identified an increased risk of death without LTx (hazard ratio [HR], 1.79; 95% CI, 1.52-2.1) and decreased LTx (HR, 0.66; 95% CI, 0.58-0.74) among individuals in the United States compared with Canada. More pronounced differences were seen in the patients in the United States with Medicaid/Medicare insurance compared with Canadians (multivariable HR for death without LTx, 2.24 [95% CI, 1.89-2.64]; multivariable HR for LTx, 0.54 [95% CI, 0.47-0.61]). Patients of nonwhite race were also disadvantaged (multivariable HR for death without LTx, 1.56 [95% CI, 1.32-1.84]; multivariable HR for LTx, 0.47 [95% CI, 0.36-0.62]).InterpretationThere are lower rates of LTx and an increased risk of death without LTx for US patients with CF with FEV1 < 40% predicted compared with Canadian patients. Findings are more striking among US patients with CF with Medicaid/Medicare health insurance, and nonwhite patients in both countries, raising concerns about underuse of LTx among vulnerable populations.

Project description:BackgroundIn 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias.ObjectiveTo use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States.DesignPopulation-based study.Setting42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers.PatientsPatients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013.MeasurementsCox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival.ResultsMedian age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P < 0.001). On the basis of contemporary data from 2009 to 2013, the median age of survival in Canada was 10 years greater than in the United States (50.9 vs. 40.6 years, respectively). The adjusted risk for death was 34% lower in Canada than the United States (hazard ratio, 0.66 [95% CI, 0.54 to 0.81]). A greater proportion of patients in Canada received transplants (10.3% vs. 6.5%, respectively [standardized difference, 13.7]). Differences in survival between U.S. and Canadian patients varied according to U.S. patients' insurance status.LimitationAscertainment bias due to missing data or nonrandom loss to follow-up might affect the results.ConclusionDifferences in cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private-insurance status among U.S. patients. Differential access to transplantation, increased posttransplant survival, and differences in health care systems may, in part, explain the Canadian survival advantage.Primary funding sourceU.S. Cystic Fibrosis Foundation.

Project description:ImportanceIn the United States, the number of deceased donor hearts available for transplant is limited. As a proxy for medical urgency, the US heart allocation system ranks heart transplant candidates largely according to the supportive therapy prescribed by transplant centers.ObjectiveTo determine if there is a significant association between transplant center and survival benefit in the US heart allocation system.Design, setting, and participantsObservational study of 29 199 adult candidates for heart transplant listed on the national transplant registry from January 2006 through December 2015 with follow-up complete through August 2018.ExposuresTransplant center.Main outcomes and measuresThe survival benefit associated with heart transplant as defined by the difference between survival after heart transplant and waiting list survival without transplant at 5 years. Each transplant center's mean survival benefit was estimated using a mixed-effects proportional hazards model with transplant as a time-dependent covariate, adjusted for year of transplant, donor quality, ischemic time, and candidate status.ResultsOf 29 199 candidates (mean age, 52 years; 26% women) on the transplant waiting list at 113 centers, 19 815 (68%) underwent heart transplant. Among heart transplant recipients, 5389 (27%) died or underwent another transplant operation during the study period. Of the 9384 candidates who did not undergo heart transplant, 5669 (60%) died (2644 while on the waiting list and 3025 after being delisted). Estimated 5-year survival was 77% (interquartile range [IQR], 74% to 80%) among transplant recipients and 33% (IQR, 17% to 51%) among those who did not undergo heart transplant, which is a survival benefit of 44% (IQR, 27% to 59%). Survival benefit ranged from 30% to 55% across centers and 31 centers (27%) had significantly higher survival benefit than the mean and 30 centers (27%) had significantly lower survival benefit than the mean. Compared with low survival benefit centers, high survival benefit centers performed heart transplant for patients with lower estimated expected waiting list survival without transplant (29% at high survival benefit centers vs 39% at low survival benefit centers; survival difference, -10% [95% CI, -12% to -8.1%]), although the adjusted 5-year survival after transplant was not significantly different between high and low survival benefit centers (77.6% vs 77.1%, respectively; survival difference, 0.5% [95% CI, -1.3% to 2.3%]). Overall, for every 10% decrease in estimated transplant candidate waiting list survival at a given center, there was an increase of 6.2% (95% CI, 5.2% to 7.3%) in the 5-year survival benefit associated with heart transplant.Conclusions and relevanceIn this registry-based study of US heart transplant candidates, transplant center was associated with the survival benefit of transplant. Although the adjusted 5-year survival after transplant was not significantly different between high and low survival benefit centers, compared with centers with survival benefit significantly below the mean, centers with survival benefit significantly above the mean performed heart transplant for recipients who had significantly lower estimated expected 5-year waiting list survival without transplant.

Dataset Information

Bridging the survival gap in cystic fibrosis: An investigation of lung transplant outcomes in Canada and the United States.

Background

Methods

Results

Conclusions

Publications

Bridging the survival gap in cystic fibrosis: An investigation of lung transplant outcomes in Canada and the United States.

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